In The Name of
God
Dr. F Behnamfar MD
Diagnosis and
treatment of gestational
trophoblastic disease
Gestational Trophoblastic
Neoplasia
A spectrum of interrelated conditions
originating from placenta:
 Complete
and partial moles
 Invasive mole
 Gestational choriocarcinoma
 Placental Site Throphoblastic Tumor
Hydatiform Moles
1
in 1500 pregnancy
 1 in 600 therapeutic
abortions
 20% will develop malignant sequelae
requiring chemotherapy
 Most will have non-metastatic molar
proliferation or invasive moles
 gestational choriocarcinomas and
metastatic disease can develop
Complete Hydatiform Moles

Some diagnosed as missed abortions
(early ultrasound without symptoms)
most patients have a clinical or
ultrasonographic diagnosis of hydatidiform
mole
 Uterine enlargement beyond the expected
gestational age in up to 50%
 may present with vaginal bleeding or
expulsion of molar vesicles

Complete Hydatiform Moles

complications of molar pregnancy, including
pregnancy induced hypertension,
hyperthyroidism, anemia, and hyperemesis
gravidarum, are more frequently seen among
patients with complete moles

15–25% of patients will have theca lutein cysts
with ovarian enlargement of more than 6 cm
Diagnoses
usually during the first trimester of pregnancy
 most common symptom: abnormal bleeding
 uterine enlargement greater than expected for
gestational age
 absent fetal heart tones
 cystic enlargement of the ovaries
 hyperemesis gravidarum
 Abnormally high level of hCG for gestational age
Gestational
choriocarcinoma
occurs in approximately 1 in 20,000–40,000
pregnancies
 50% after term pregnancies
 25% after molar pregnancies
 remainder after other gestational events
Placental site trophoblastic tumors can
develop after any type of pregnancy
Molar Pregnancy
 Usually
diagnosed during first trimester
 Most common symptom abnormal
bleeding
 Ultrasonography has replaced all other
diagnostic procedures
 Findings may be subtle in cases of early
complete or partial mole
 Suction curettage is the best type of
uterine evacuation
Follow up
 Serial
hCG values, as long as decreasing
no role for chemotherapy
 AUB
more than 6weeks after any kind of
pregnancy should be evaluated with hCG
Diagnoses of Malignant Sequele
 Increasing
hCG levels (Increase of three
values > 10% over 2 weeks ) or plateau
(four values ± 10% over 3 weeks )
 Histologic diagnoses of Choriocarcinoma
or invasive mole from uterine currettage
 Clinical or radiographic evidence of
metastases
Gestational Trophoblastic
Neoplasia

Staging
Nonmetastatic (I)
Metastatic(II-IV)

FIGO Scoring
Low risk (Total score<7)
High risk (Total score>7and =7)

Clinical classification of NCI
Poor-prognosis metastatic
gestational trophoblastic
disease(NCI)
 Any
risk factor:
 Long duration (z4 months
since last pregnancy)
 Pretherapy hCG level z40,000 mIU/ml
 Brain or liver metastases
 Antecedent term pregnancy
 Prior chemotherapy
FIGO scoring system




Age(years)
Antecedent pregnancy
Interval from index pregnancy (months)
Pretreatment human chorionic gonadotropin level
 Largest tumor size including uterus (cm)
 Site of metastases
 Number of metastases identified
 Previous failed chemotherapy
FIGO Scoring System
Treatment of low risk GTN





Variety of agent :MTX,Actinomycin D
,Etoposide,5FU and Cisplatinum
Early hysterectomy shortens the duration and
amount of chemotherapy to produce remission
Alternative single agent if plateu or increasing
hCG
Multiagent regimen if alternative single agent
failes
100% curable
Methotrexate
 Li
et al,1956,First treatment of metastatic
GTN
 1964,Bagshawe,administration of folinic
acid, reducing toxicity
 1976, Bagshawe, mutch better response
to single agent MTX for nonmetastatic
 Other drugs tested, more toxic
Chemotherapy
 Single
agent MTX therapy
Nonmetastatic
Low risk metastatic
 Multi agent regimens
resistance to MTX
initially high risk tumors
MTX single agent protocols
 MTX
alone, 5days,0.4mg/kg/day
 MTX alone,one inj. weekly,30 -50mg/m2
 MTX with folinic acid ,MTX 1mg/kg/day
folinic acid 0.1mg/kg/day,every other
day,8days regimen
 MTX with folinic acid ,MTX100mg/m2 IV
bolus,followed by 200mg/m2/12h and
folinic acid
Strategies for further courses
 Regular
 Single
administration every 7-14 days
systematic course, further courses
depending on HCG decrease(if plateau or
reelevatd
Change of chemotherapeutic agent
 Stable
hCG for three consecutive weeks
 Re-elevated
 Not
hCG
falling at least one log within 18 days
of first treatment
Remission and Relapse
 Remission
:hCG level within normal range
for at least three consecutive weeks
 Relapse
:Rising hCG after remission
MTX Toxicity
 Hepatotoxicity
 GI
disturbances
 Granulocytopenia
 Thrombocytopeni
 Mucositis
Demographic praperties of low risk GTN
case
vali. Ase Hospital TUMS
Age
Min
max
Mean
Gravid
1
11
3.2
4
0.4
Abortion 0
Staging of low risk GTN case
vali. Ase Hospital TUMS
88
90
80
70
60
50
40
30
20
10
0
10.5
1.5
I
II
III
FIGO Score of low risk GTN case
vali. Ase Hospital TUMS
43.9
45
40
35
30
25
20
15
10
5
31.8
13.5
4.5
3
1.5
0
zero
I
III
III
IV
V&VI
Toxicity of MTX in low risk GTN case
vali. Ase Hospital TUMS
18
16
14
12
10
8
6
4
2
0
17.2
7.8
2
He
He
Na
pa
ma
us
tox
ea
tox
icit
vo
icit
mi
y
y
tti n
g
Failure Frequency of low risk GTN case
vali. Ase Hospital TUMS
80
70
60
50
40
30
20
10
0
72
11
17
0
co
to x
r es
r el
mp
ap
icit
ista
se
l et
y
nt
er
em
iss
i on
Results
Failure frequency :18

Initial resistance

Relapse

Toxicity
(28%)
11 (17%)
0
7
(11%)
Methods
 Retrospective
study,1996-2006 Valie-Asr
 Low risk GTN(metastatic and
nonmetastatic)
 Single agent weekly pulse MTX 3050mg/kg
 Questionare from files and telephoning to
patients
Results
 66
low risk GTN cases(58 nonmetastatic
and 8 metastatic)
 97%
following molar pregnancy and 3%
following abortion
Toxicity
 %7.8
Hepatotoxicity
 %17.2 GI disturbances
 %2 Granulocytopenia
 No Mucositis
Second Line of treatment
 Pulse
 18
Actinomicin(1.25mg/m2)Biweekly
cases
 %100
Response
Time to Negative Beta hCG
 First
line
 Second
7.18+_3.5 weeks
line 21+-weeks
BhCG Level
 Resistant
Group :16937 mIu/ml
 Response
Group :8056 mIu/ml
 Pulse
MTX,72% remission rate with low
toxicity
 Actinomycin as second line,%100 cure of
MTX resistant and toxic group
 Prolonged regression of HCG in resistant
group
 Higher HCG level in resistant group
Discussion
New England Center of Boston(1984)
(Only nonmetastatic)
 8 days regimen (MTX-FA)
 88% remission rate
 1.2 cycles in average
 14% Hepatotoxicity
 6% granulocytopenia
Discussion
Jaice S. Kwon et al (2001)
 Weekly IV Methotrexate 100mg/m2 with
folinic acid (nonmetastatics)
 45.5% respnse rate (Folinic acid may be
detrimental)
 Low toxicity ( no change of treatment )
 Only significant prognostic factor
pretreatment hCG level
Discussion
Gleeson 1993,Hoffman1996,Homsely
1988(GOG)
Weekly pulse MTX
73-89% complete response
30% GI disturbance ,20% lucopenia
Advantages
 Outpatient
administration
 Patient convenience
 Minimal systemic toxocity
 Low cost
 Comparable efficacy to other first-line
treatments
Thanks